Effect of Platelet GPIIb/IIIa Receptor Blockade With MK383 on Infarct Size and Myocardial Blood Flow in a Canine Reocclusion Model

Abstract

Platelet activation and aggregation during ischemia influence reperfusion-related myocyte necrosis, myocardial perfusion at the microvascular level, and thereby eventual recovery of cardiac performance. Inhibition of platelet activity therefore represents a worthwhile target to reduce cellular injury. The current study examined the effects of MK383 (tirofiban), a potent inhibitor of platelet aggregation, on infarct size and myocardial perfusion in canine subjects to either reocclusion (ie, 120-minute + 60-minute ischemia with intervening reperfusion) or prolonged occlusion (ie, 3 hours) followed by reperfusion (180 minutes). Platelet aggregation, infarct size (tetrazolium staining), coronary blood flow (flow probe), coronary vascular reserve, and myocardial perfusion (microspheres) were evaluated. MK383, administered at the time of reperfusion, produced a modest reduction of tissue necrosis (compared to saline-treated controls) in the reocclusion and prolonged occlusion studies. Blood flow in the infarct-related artery after coronary occlusion was comparable between treatment groups, as was myocardial perfusion in the deeper layers of the ischemic region; coronary vascular reserve decreased progressively during reperfusion. Of note, compensatory changes in blood flow within the adjacent nonischemic myocardium were not observed. In conclusion, we report that that limiting platelet aggregation during reperfusion impacted infarct development. Continued investigation into the mechanisms by which inhibition of platelet activity protects myocardium against ischemia–reperfusion injury and improves clinical outcomes is necessary.

Therapeutic effect of pre-operative tirofiban on patients with acute ischemic stroke with mechanical thrombectomy within 6–24 hours

“…6 In a MR CLEAN subgroup analysis, Mulder et al found that prior treatment with oral daily antiplatelet drugs did not increase the occurrence of death, sICH, or other safety concerns, and may instead improve functional outcome. 7 Another study evaluated the relationship of prior aspirin use with early efficacy and safety outcomes in patients with emergent large vessel occlusion (ELVO) treated with MT, and indicated that antiplatelet pre-treatment does not increase the risk of sICH and may independently improve functional independence. 8 However, the peak concentrations and onset rates of oral antiplatelet drugs are low, thus they are not suitable for first aid in AIS.…”

Acute Myocardial Infarction: Perspectives on Physiopathology of Myocardial Injury and Protective Interventions

“…glycoprotein 2b/3a blockers, etc.) have also reported significant anti-necrosis and anti-arrhythmic effects [82,83]; however, cardioprotective efficacy of these agents may be limited with extended ischemic durations [84].…”

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“…Therefore, antiplatelet therapy is indispensable in operation. Studies have shown that tirofiban can effectively improve myocardial perfusion in patients and reduce the incidence of postoperative complications (Kingma, 2019). Tirofiban is a highly effective and reversible GP b/a inhibitor, which can prevent platelet aggregation.…”